Salicylic Acid → HCID 67413337, compound

HRID 1897428Notes

Reaction equation

HRID 1897428 reaction equation
[OH:1][C:2]1[CH:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4](O)=O.[C:11]([O-:14])([O-])=[O:12].[Cs+].[Cs+].CC(C)(C(=O)CC(=O)C(C)(C)C)C.Br[C:31]1[CH:32]=[C:33]2[C:37](=[CH:38][CH:39]=1)[N:36]([CH2:40][CH:41]([CH3:43])[CH3:42])[N:35]=[CH:34]2>CN1C(=O)CCC1.Cl[Cu]>[CH2:40]([N:36]1[C:37]2[C:33](=[CH:32][C:31]([O:1][C:2]3[CH:10]=[CH:9][CH:8]=[CH:7][C:3]=3[CH2:4][C:11]([OH:14])=[O:12])=[CH:39][CH:38]=2)[CH:34]=[N:35]1)[CH:41]([CH3:43])[CH3:42]

Participants

7

Reactant 4

HCID 338Salicylic AcidHCID 10796Cesium carbonateHCID 707002,2,6,6-Tetramethyl-3,5-heptanedioneHCID 21894750HCID 21894750, compound

Product 1

HCID 67413337HCID 67413337, compoundYield 36.3%

Reagents, catalysts & solvents 2

HCID 62652Cuprous chlorideCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent2×

Conditions

Temperature
145 °C

Procedure

To a degassed suspension of 2-hydroxybenzoic acid (2.4 g, 15.8 mmol) and Cs2CO3 (7.72 g, 23.7 mmol) in NMP (13 mL), 2,2,6,6-tetramethyl-heptane-3,5-dione (0.41 mL, 1.97 mmol) and compound 14p (2.0 g, 7.90 mmol) was added followed by small amount of NMP for rinsing. The resulting mixture was degassed again with nitrogen and then CuCl (0.39 g, 3.95 mmol) was added and reaction again degassed. The mixture was heated to 140-150° C. After mixing for 22 hours, the reaction mixture was poured into ether/H2O. The two layers were separated and the aqueous layer (pH ˜11) was washed with ether. The aqueous layer was acidified to pH 7 and extracted with ether (4×) and the combined organic layers were dried over anhydrous Na2SO4. The solvent was removed under reduced pressure. The precipitate was formed gradually in a small volume of a mixed solvent of ether/hexane/DCM and collected through filtration to obtain the desired compound (15p) (0.93 g, 36% isolation yield). 1H NMR (400 MHz, CDCl3) δ 7.87 (br s, 1H), 7.38-7.28 (m, 2H), 7.25-7.17 (m, 2H), 7.13 (d, J=9.39 Hz, 1H), 7.10-7.03 (m, 1H), 6.79 (d, J=8.61 Hz, 1H), 4.15 (br s, 2H), 3.79 (s, 2H), 2.40-2.27 (m, 1H), 0.93 (s, 3H), 0.92 (s, 3H); MS (APCI+) m/z 325 (M+H), MS (APCI−) m/z 322.8 (M−H) and 646.8 (2M−H) detected.

Workup

  1. additionwas added
  2. washfor rinsing
  3. customThe resulting mixture was degassed again with nitrogen
  4. customreaction
  5. customagain degassed
  6. additionAfter mixing for 22 hours
  7. additionthe reaction mixture was poured into ether/H2O
  8. customThe two layers were separated
  9. washthe aqueous layer (pH ˜11) was washed with ether
  10. extractionextracted with ether (4×)
  11. dry with materialthe combined organic layers were dried over anhydrous Na2SO4
  12. customThe solvent was removed under reduced pressure
  13. customThe precipitate was formed gradually in a small volume of a mixed solvent of ether/hexane/DCM
  14. filtrationcollected through filtration

Sources & evidence

ORD record
ord-4d45582c2aeb40d199dd261d2a5afaa9
Source dataset
uspto-grants-2013_08
Patent number
US08518983B2

Reaction notes

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